Mosquito-borne encephalitis viruses are endemic zoonoses that continue to pose a health risk to the residents of California and other affected areas of the United States. Our proposed research investigates how vertebrate and invertebrate host-virus relationships may affect the force of transmission and virus persistence. Experiments compare the responses of different avian host species and the primary vector mosquito, Culex tarsalis, to infection with the Alphavirus western equine encephalomyelitis virus (WEE) and the Flavivirus St. Louis encephalitis virus (SLE) and investigate how these interactions may lead to the introduction or emergence of new viral genotypes. Research addresses the following interrelated specific hypothesis: 1. Vertebrate host competence factors of survival, viremia and antibody production impact the force of WEE and SLE transmission. Experimental infection studies will compare the viremia responses of avian species that are abundant and have relatively high, low or negative seroprevalence rates in nature. 2. Virus infection negatively affects the vector competence and bionomics of Cx. tarsalis. The impact of the infecting dose of WEE and SLE on mosquito pathology, susceptibility to infection, transmission, life table parameters and flight behavior will be assessed experimentally using colonies selected for increased and decreased susceptibility to infection. 3. WEE and SLE respond to vertebrate and vector host defenses by establishing chronic infections and/or by changing genetically. Experiments will attempt to establish chronic infections in representative resident and migrant bird species to assess their ability to maintain virus overwinter, to disperse virus to new susceptible populations, or to alter virus genetics. Studies will assess how alternating sequential infections between vertebrate and vector species that are part of the natural transmission cycle may alter virus genetics and fitness.